This proposal requests support for a predoctoral and postdoctoral Training Program in Pediatric Hematologic and Oncologic Diseases in the Cincinnati Children's Hospital Medical Center (CCHMC), University of Cincinnati College of Medicine. The underlying premise of this Training Program is that there is a recognition of and need to address the lack of individuals trained in therapeutic research on pediatric hematologic and oncologic diseases who also have a deep appreciation for taking scientific discovery into the clinic. Therefore, the goal of the Training Program is to provide a rigorous understanding of the basic mechanisms of pediatric hematologic and oncologic diseases with a clear translational focus. The program draws heavily upon integrated, m ultidisciplinary, innovative, and established graduate progr ams, Ph.D. postodoctoral training programs, and clinical fellowship training programs from 7 divisions within CCHMC, and involves 21 NIH funded basic scientists and physician-scientists as core mentoring faculty and 5 ancillary clinical faculty. This program enrolls promising young doctoral and postdoctoral (2 predoctoral and 4 postdoctoral) candidates, with a emphasis on minority candidate recruitment, to specialize on one of the hematology and oncology research areas under the direct mentorship of a core mentoring faculty and an ancillary clinical faculty. The areas of research include pediatric hematologic diseases such as leukemia, Fanconi anemia, myeloproliferative disorders, coagulation disorders, and sickle cell disease, immuno- deficiency disorders such as X-linked lymphoproliferative disorder, severe combined immunodeficiencies, Wiskott-Aldrich syndrome, and common variable immunodeficiency, molecular gene therapy strategies treating Fanconi anemia, storage diseases, and sickle cell anemia, and targeted therapies against childhood cancers such as leukemia/lymphoma, neuroblastoma, sarcomas, and musculoskeletal tumors. The selected program faculty share research interests and have a history of collaboration in studies of various blood- related research activities, yet they approach hematologic and oncologic diseases and therapeutics from different perspectives. The use of mouse models combined with patient-directed initiatives represents one of the unique strengths of the Training Program. The grant will include an administrative core consisting of the Principal Investigator, Co-Pi, an Executive Committee, an Admission Committee, an Advisory Committee, and an External Advisory Committee. Training will combine a series of required curriculum including an ethical education course, Experimental Hematology, Immunological Mechanisms of Diseases, Action of Cancer Therapeutics, and Translational Trial Development and Support Laboratory Educational Activities, as well as a number of electives including Biostatistics, Clinical Trials, Functional Genomics, and Seminar in Drug Development. Regular research retreats, data clubs, journal clubs, and seminar series will serve to complement the mentor-directed research activities by further enhancing the knowled ge base of the trainees and cohesiveness of the program. The progress of each trainee will be reviewed and evaluated semi- annually.